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Total organic carbon (TOC) is an important parameter for characterizing shale gas and oil reservoirs. Estimation of TOC from well logs has previously been achieved by an empirical model. The radial basis function (RBF) neural network is a new quantitative method that can generate a smooth and continuous function of several input variables to approximate the unknown forward model. We investigated the basic principles of the RBF including network structure, basis function, network training method, and its application in the TOC prediction. The nearest neighbor algorithm was selected for the network training. Then, the Gaussian width was investigated to improve the TOC prediction accuracy through leave-one-out cross-validation. Finally, field cases of organic shale were studied for the TOC prediction, and the prediction results using the RBF method were compared with those of the [Formula: see text] method. Furthermore, according to sensitive attribute ranking, the impacts of different input logs on the predicted results were also investigated through various experiments, and the best network model was finally chosen. The error analysis between the prediction results and lab-measured TOC in some examples indicated that the new approach is more accurate than a single empirical regression method and more flexible than the [Formula: see text] method.